1. Field of the Invention
At least one embodiment of the invention relates to a cardiac stimulator for the delivery of cardiac therapy.
2. Description of the Related Art
Implantable cardiac stimulators in the form of cardiac pacemakers or cardioverters/defibrillators are typically connected to electrode leads which comprise stimulation electrodes and defibrillation electrodes—the latter of which may be provided in addition thereto, as an option—in a ventricle or in the immediate vicinity. Using a stimulation electrode, a cardiac pacemaker can deliver an electrical stimulation pulse to the muscle tissue of a ventricle to thereby induce a stimulated contraction of the ventricle provided the stimulation pulse has sufficient intensity and the cardiac muscle tissue (myocardium) is not in a refractory phase at the moment. Such a stimulated contraction of a ventricle is referred to as a stimulated event within the scope of this description. If a natural contraction of the ventricle occurs, this is referred to as natural action or a natural or intrinsic event within the scope of this description. A contraction of the right atrium of a heart, for instance, is referred to as an atrial event, which can be a natural atrial event, for instance, or—in the case of an atrial cardiac pacemaker—can also be a stimulated atrial event. In the same sense, a distinction can be made between natural (intrinsic) and stimulated left ventricular events and right ventricular events.
Local excitation of the myocardium propagates from the excitation site by conduction in the myocardium, resulting in depolarization of the muscle cells and thus contraction of the myocardium. After a brief period of time the muscle cells are repolarized and the myocardium therefore relaxes. During the phase of depolarization, the cardiac muscle cells are insensitive to excitation, i.e. they are refractory. This period is referred to as the refractory period. The electrical potentials associated with depolarization and repolarization can be sensed, and the variation thereof over time—referred to as an electrocardiogram—can be evaluated.
The cardiac rhythm of a healthy individual is determined by the sinoatrial node, which is controlled by the autonomic nervous system. It excites—via conduction—the right atrium of a human heart and furthermore, via the AV node, the (right) ventricle of the heart. A natural cardiac rhythm originating in the sinoatrial node is therefore also referred to as sinus rhythm and induces natural contractions of the particular ventricle, which can be detected as natural (intrinsic) events.
Such natural (intrinsic) events are detected by determining the electrical potentials of the myocardium of the particular ventricle using sensing electrodes, which are part of a corresponding electrode lead. The sensing electrodes can also be the stimulation electrodes, and can be used in alternation as stimulation electrodes and as sensing electrodes. Typically, a pair of sensing electrodes composed of two adjacent electrodes, i.e. a tip electrode and a ring electrode, is provided for the sensing, wherein the tip electrode is also used as the stimulation electrode. A bipolar recording of an intracardial electrocardiogram (IEGM) is obtained in this manner. In that case, sensing and stimulation take place in the ventricle using a ventricular electrode lead, and stimulation and sensing take place in the atrium (the right atrium) using an atrial electrode lead which is connected separately to the particular cardiac stimulator. In addition, a left ventricular electrode lead can be provided, which typically extends via the coronary sinus and a lateral vein branching off therefrom into the vicinity of the left ventricle, where it can comprise a stimulation electrode and/or sensing electrode having a small surface area.
During operation of the cardiac stimulator, the sensing electrodes are connected to appropriate sensing units which are designed to evaluate a particular electrocardiogram recorded using a sensing electrode (or a pair of sensing electrodes), and, in particular, to detect intrinsic atrial or ventricular events, i.e. natural atrial or ventricular contractions. This takes place, for example, by comparison with a threshold value, i.e. an intrinsic event is detected when a particular intracardial electrocardiogram exceeds a suitably specified threshold value.
On the basis of the frequency at which the atrial and ventricular events follow one another, the particular intrinsic atrial heart rate (atrial frequency) or ventricular heart rate (ventricular frequency) can be derived, thus enabling detection of tachycardias, for example.
In the case of known demand pacemakers, the detection of natural events is also used to suppress (inhibit) the delivery of stimulation pulses to a particular ventricle if the natural event is detected within a time window before the planned delivery of a stimulation pulse to the ventricle. In the case of rate-adaptive cardiac pacemakers, the point in time for delivery of a particular stimulation pulse is planned depending on a particular stimulation rate, which should correspond to a patient's physiological demand, and is higher when exertion is greater, for instance. For this purpose, a cardiac stimulator can be equipped with one or more activity sensors, which can be a CLS sensor, for instance, which is described in greater detail below.
The natural effect of the autonomic nervous system on the heart rate, which is simulated by a rate-adaptive cardiact stimulator, is referred to as chronotropism.
Cardiac performance is determined by chronotropism as well as contractility, the influencing of which is referred to as inotropism.
To determine the contractility of a heart, it is known to install an impedance or conductivity meter in a housing of a cardiac stimulator (e.g. an implantable cardiac pacemaker), which is designed to generate a unipolar or bipolar signal indicating the variation of impedance or conductivity. For this purpose, a plurality of impedance or conductivity values or a related variation in impedance or conductivity can be measured during at least one cardiac cycle. This takes place either in a unipolar manner by performing a measurement between a neutral electrode and a measuring electrode, or between two measuring electrodes. In addition, an evaluation unit is disposed in the housing, which is used to evaluate the variation in impedance or conductivity, and to determine a contractility value on the basis of the variation in impedance or conductivity. Electrotherapeutic devices that can determine the contractility of a heart can be used to adapt a therapy to be delivered by the electrotherapy device to the particular contractility state of the patient's heart.
As indicated, contractility describes an inotropic state of a heart. Contractility influences the force and speed of a myocardial contraction. Contractility is controlled by three mechanisms:                direct control by the autonomic nervous system (ANS),        the so-called Starling mechanism, and        the so-called Bowditch effect (force-frequency coupling).        
The main mechanism, the control of circulatory regulation by the autonomic nervous system, increases contractility and heart rate when metabolic demand is elevated e.g. during physical or mental exertion, to ensure suitable blood supply. In a healthy individual, the inotropism of the heart therefore causes contractility to increase due to increased physiological demand.
In patients with chronic heart failure (CHF), myocardial contractility decreases to a low level, and interventricular synchronization is worsened. This is accompanied by a low ejection fraction (EF), and by a low quality of life and high mortality. HF occurs frequently in the population. Recently, HF patients have been treated with resynchronization therapy devices, such as 3-chamber cardiac pacemakers or defibrillators. The objective of such pacemaker therapy is to synchronize the two ventricles of a heart using biventricular stimulation in order to improve the time behavior of the ventricles and, therefore, cardiac performance. Such therapy is also referred to as cardiac resynchronization therapy (CRT). Cardiac resynchronization therapy (CRT) is adequately known.
Since the contractility of the heart is controlled physiologically by the autonomic nervous system, the detection of contractility can also be utilized to adjust a physiologically adequate stimulation rate in the case of rate-adaptive cardiac pacemakers. This type of stimulation rate control, which was addressed above, is also known as closed loop stimulation (CLS).
For CLS, the intracardial variation in impedance is measured after the onset of ventricular contraction. The measurement is performed for intrinsic events and stimulated events. There is a direct dependence between the right-ventricular variation in impedance and contraction dynamics. In turn, contraction dynamics are a parameter for stimulation of the heart by the sympathetic nervous system.
As stated, closed loop stimulation is used to control the stimulation rate in the case of a rate-adaptive cardiac pacemaker.
It is known to use cardiac contractility modulation (CCM) to increase the contractility of a ventricle.
Systems for CCM therapy are known from publications such as US 2010/0069977 A1, US 2010/0069980 A1, US 2010/0069984 A1 and US 2010/0069985 A1. A system such these comprises a stimulation pulse generator which is connected to three electrodes, one of which is disposed in the atrium and two of which are disposed at the septum of the right ventricle of a patient during operation. The therapeutic principle is based on delivery of biphasic stimulation pulses with an amplitude of 7-10V and a total pulse duration of ˜20 ms in the absolute refractory period of the ventricle, with the objective of increasing contractility. The therapy is delivered for certain units of time throughout the day (e.g. 1 h on, 1 h off).
The principle of cardiac contractility modulation therapy is also described, inter alia, in U.S. Pat. No. 6,317,631 B1.
The effect of CCM therapy is based—according to current speculation—on a modification of cellular calcium ion exchange and therefore results in increased contraction force, which should also deliver a therapeutic benefit if atrial fibrillation is present. Although this has not been proven clinically, it can be explained pathophysiologically.
US 2010/0069977 A1, US 2010/0069980 A1, US 2010/0069984 A1, US 2010/0069985 A1 describe methods for delivering CCM stimulation on demand. The documents provide general descriptions of the use of physiological sensors, renal or cardiac function sensors, electrolyte sensors, serum sensors (e.g. creatinine), neurosensors (vagus nerve, sympathetic nervous system), adverse event detectors, worsening heart failure sensors, MRT sensors, activity sensors, sleep apnea sensors, ischemia sensors, sensors for metabolic demand and infarct sensors, and CCM controls that are dependent on cardiac rhythm. The stated prior art also describes a disabling of the CCM therapy when atrial fibrillation or atrial arrhythmia is detected (see US 2010/0069977 FIG. 20A and [0332]). It also provides a general description of the possible combination of CCM with other forms of stimulation and electrotherapy, such as CRT, ICD and neurostimulation.